Consequences of in utero exposure to Zika virus in offspring of AG129 mice.

ABSTRACT

Zika virus (ZIKV) can cause various diseases in offspring after congenital infection. The purpose of this study was to identify disease phenotypes in pups exposed to ZIKV in utero. Female interferon-α/ß, -γ receptor knockout mice (AG129) were infected intraperitoneally with ZIKV 7.5 days' post coitus (dpc). Viral RNA, antigen and infectious virus were detected in some, but not all, maternal and fetal tissues at various times during gestation. Fetuses of infected dams had significant intrauterine growth restriction (IUGR), which was more pronounced as females neared parturition. Pups born to infected dams were significantly smaller and had significantly shortened skull lengths, as determined by measurement with a caliper and by micro-CT analysis, as compared with age-matched controls. Growth rates of exposed pups after birth, however, was similar to sham-exposed offspring. Viral RNA was detected in pups of infected dams after birth. A lower survival rate was observed in neonates exposed to ZIKV in utero. A mortality rate of over 50%, attributed to consequences of ZIKV infection, occurred after birth in pups born to infected dams. A transient hearing loss was observed in some animals exposed to virus in utero. No motor deficits or cognitive deficits were detected using running wheel or viral paresis scoring assays. Abnormalities in offspring included smaller size, shorter skull length and increased neonatal mortality, while the only functional deficit we could detect was a low incidence of transient hearing loss.